Neoadjuvant Treatment with Pembrolizumab Improves Pathologic Complete Response Rates for Patients with Triple-Negative Breast Cancer with Lymph Node Involvement

SAN ANTONIO — The addition of the anti-PD-1 immunotherapeutic pembrolizumab (Keytruda) to neoadjuvant chemotherapy increased the rates of pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC) who had lymph node involvement, according to results from the KEYNOTE-522 trial, which were presented at the San Antonio Breast Cancer Symposium, held Dec. 10-14.

Results on pCR rates from this trial were previously presented at the European Society of Medical Oncology annual meeting, held earlier this year. The latest data presented here included subgroup analyses of patients with lymph node involvement.

“TNBC is an aggressive subtype of breast cancer with a higher recurrence rate within the first five years after diagnosis compared to other subtypes,” said Peter Schmid, MD, PhD, professor of cancer medicine at Barts Cancer Institute in London. “It has been known for some time that involvement of lymph nodes is associated with an even higher risk of recurrence in patients with TNBC.”

The current standard of care for early-stage TNBC is chemotherapy. Large analyses have demonstrated that patients who have a pCR to neoadjuvant chemotherapy have a positive outlook with very low rates of recurrence, particularly in patients with more aggressive cancers like TNBC, explained Schmid.

“Currently, the pCR rate for standard chemotherapy treatment using an anthracycline and taxane combination is about 40 percent, or about 50 percent if a platinum-based drug is added to the combination,” added Schmid. “There continues to be a significant need for new regimens that can increase the pCR rate and increase long-term, event-free survival for patients with TNBC.”

In this study, Schmid and colleagues examined the effect of adding the immune checkpoint inhibitor pembrolizumab to neoadjuvant chemotherapy and adjuvant therapy in patients with early-stage TNBC. Treatments targeting the PD-1/PD-L1 pathway were previously shown to be effective for patients with metastatic TNBC.

The study enrolled 1,174 patients, aged 18 years or older, with previously untreated, non-metastatic, centrally confirmed TNBC. Patients were randomly assigned 2:1 to receive either pembrolizumab plus chemotherapy or placebo plus chemotherapy as neoadjuvant treatment. After neoadjuvant treatment, patients underwent definitive surgery and received radiation therapy as indicated. Patients received either adjuvant pembrolizumab or placebo until recurrence or unacceptable toxicity. The primary endpoints of the study, which is ongoing, are pCR and event-free survival.

Schmid and colleagues have previously reported that patients in the pembrolizumab plus chemotherapy arm had a significantly higher rate of pCR compared to patients in the chemotherapy alone arm (64.8 percent vs. 51.2 percent), regardless of PD-L1 expression.

The latest data presented here showed that among patients whose cancers had spread to the lymph nodes, 64.8 percent of those in the pembrolizumab plus chemotherapy arm had a pCR, compared to 44.1 percent in the chemotherapy only arm. High rates of pCR were also observed in patients with stage III disease.

“Our results suggest that adding pembrolizumab to neoadjuvant chemotherapy is beneficial for patients with the most aggressive disease and the highest unmet need,” said Schmid. “I think the results have the potential to be practice-changing.”

A limitation of the study is that event-free analyses are still preliminary, as the study is ongoing.

“After 15 months of follow-up, we see a strong favorable trend for event-free survival, but it has not yet met the predefined boundaries of statistical significance,” said Schmid. “Additional analyses will follow in the near future.”

This study was sponsored by MSD. Schmid has received research support from AstraZeneca, Genentech, Roche, OncoGenex Pharmaceuticals, Novartis, Astellas, and Medivation and has received honoraria or consultation funds from Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, and Puma.